This clinical research proposal is part of an interactive application of four R01's designed to discover new systemic therapies against breast cancer. This project will validate in the clinic promising new antineoplastic chemotherapy and combinations of new chemotherapy and modulating agents (Vitamin D3 and Retinoid acid analogs) developed in experimental in-vitro and in-vivo models against breast cancer in the other three R01's of this application. Specifically, we will conduct: a) Phase II efficacy studies of new chemotherapy in advanced breast cancer after successful completion of Phase I clinical and pharmacologic studies of these agents; b) Phase I clinical and pharmacologic studies of new drug combinations in advanced breast cancer; c) Phase II efficacy studies of new drug combinations in advanced and previously untreated breast cancer; d) correlations of observed antitumor effects and toxicities with pharmacokinetic parameters and the pharmacokinetic interactions of new drug combinations; e) correlations of preclinical and clinical observations by the integration of the work performed under this clinical project and the other three preclinical R01's. All clinical trials will be conducted under strict control conditions to include peer review for scientific merit, review and approval of protocol by institution's IRB and granting agency, careful coordination of needed diagnostic and laboratory procedures, prospective data collection, weekly review of clinical data, interim analysis of results and intense quality assurance review by our Cancer Center Clinical Trials Office. We anticipate that this research has a significant chance of having a positive impact in the treatment of breast cancer in humans.